No abstract

The developed nanoparticles might drive antigens to be presented through MHC class I and II molecules to both CD8(+) and CD4(+) T cells, favoring a complete and coordinated immune response.

The use of morphine applied topically to painful wounds has potential advantages, such as dose reduction, fewer side effects and compound formulations, have been proposed for this purpose. Given the potential high impact of drug product quality on a patient’s health, the aim of the present study was to develop two stable sterile hydrogels containing morphine hydrochloride, intended for topical application on painful wounds. Two carboxymethylcellulose sodium-based hydrogels were prepared containing 0.125% w/w (F1-MH semi-solid formulation) and 1.0% w/w (F2-MH fluid formulation) morphine hydrochloride (MH), respectively. Studies included a risk assessment approach for definition of the quality target product profile (QTPP) and assessment of critical quality attributes (CQA) of the hydrogels to support product quality and safety. Safe, odourless, yellowish, translucent and homogeneous gels were obtained, with suitable microbiological and pharmaceutical characteristics. The active substance concentration was adapted according to the characteristics of the dose-metering device. Release profiles were investigated using Franz diffusion cells, and characterised by different kinetic models. Increasing gel viscosity prolonged drug release, with rates of 17.9 ± 2.2 μg·cm−2·h−1 (F1-MH) and 258.0 ± 30.4 μg·cm−2·h−1 (F2-MH), allowing for the reduction of the number of applications and improving patient compliance. The gels proved to be stable for up to 60 days at room temperature. The semi-solid and fluid MH-containing hydrogel formulations are safe, stable and suitable for use in hospital settings, which is rather important for wound-related pain management in cancer palliative care or burn patients.

Non-steroid anti-inflammatory drugs (NSAIDs), such as etofenamate, are among the most prescribed drugs used for their analgesic, anti-rheumatic, antipyretic and anti-inflammatory properties. Topical formulations have the main advantage of targeted delivery. However, drugs must overcome the skin due to its role as a physical and chemical barrier against the penetration of chemicals and microorganisms. This barrier must be altered to allow the permeation of drugs at a suitable rate to the desired site of activity. Permeation modulators can intercalate the skin outer layers causing structure disruption, opening an energetically favourable route for the drug to diffuse through. The aim of this work was the development of hydroalcoholic gels containing 5.0% (w/w) of etofenamate for topical administration with anti-inflammatory activity and enhanced drug delivery. The physical and chemical characterization, in vitro release and permeation studies and in vivo anti-inflammatory activity were assessed. The gel with 30% ethanol showed in vivo anti-inflammatory activity with suitable physical chemical and microbiologic characteristics. In vitro release and permeation studies revealed that the different amounts of ethanol used influenced the release profiles of etofenamate. Moreover, it was demonstrated that this formulation is an adequate vehicle for the etofenamate skin permeation.

The barrier properties of the stratum corneum (SC) are largely dependent on the intactness of the lipid lamellae that surround the corneocytes. Ceramides, fatty acids, and cholesterol together with hydrocortisone (HC) have thus been proposed as protective or therapeutic agents against xerosis and atopic dermatitis (AD). However, topical delivery of these substances is still a challenge because of the excellent barrier function of the skin. The aim of the present study was to develop a formulation with combined anti-inflammatory/barrier repair properties. In order to achieve this goal, a new non-ionic O/W emulsion (CerEmulsion) containing skin barrier lipids and HC was prepared. Its physicochemical and microbiological stability and skin permeation performance were compared to a blank emulsion (NoCerEmulsion). Placebos described as PlaceboCerEmulsion and PlaceboNoCerEmulsion of CerEmulsion and NoCerEmulsion, respectively, were also prepared in order to study the transepidermal water loss (TEWL) profiles. The emulsions presented white glossy and pourable characteristics with an acidic pH. CerEmulsion showed smaller droplet sizes and higher viscosity values (5000 mPas) while NoCerEmulsion presented viscosity values of 2000 mPas. Crystalline structures were prominent in both emulsions. The microbiological analysis showed that the results were within the established specification limits. CerEmulsion and NoCerEmulsion have shown similar release profiles and CerEmulsion presented a similar anti-inflammatory activity in vivo when compared with a commercially available 1% HC emulsion. Both emulsions were chemically, physically, and microbiologically stable. TEWL was significantly lower for the group treated with PlaceboCerEmulsion, suggesting that skin hydration was higher with this ceramide-containing formulation.Practical applications: In this work, the authors develop and characterize a new non-ionic HC/ ceramide-dominant O/W emulsion as a topical therapy for the improvement of skin barrier abnormalities in atopic dermatitis (AD). This unique formulation includes high concentrations of three lipids (ceramides, cholesterol, and free fatty acids) and paraffin. Its use is recommended for AD patients !6 months of age. It is also indicated for the management and relief of burning and itching associated with various dermatoses, including AD, irritant contact dermatitis, and radiation dermatitis.